Core sepsis-related competencies for medical students: an international consensus by Delphi technique.

BACKGROUND: Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. METHODS: Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13-18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. RESULTS: The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. CONCLUSION: Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess.

A cost-minimization analysis was conducted for Klebsiella pneumoniae liver abscess (KLA) patients enrolled in a randomized controlled trial which found oral ciprofloxacin to be non-inferior to intravenous (IV) ceftriaxone in terms of clinical outcomes. Healthcare service utilization and cost data were obtained from medical records and estimated from self-reported patient surveys in a non-inferiority trial of oral ciprofloxacin versus IV ceftriaxone administered to 152 hospitalized adults with KLA in Singapore between November 2013 and October 2017. Total costs were evaluated by category and payer, and compared between oral and IV antibiotic groups over the trial period of 12 weeks. Among the subset of 139 patients for whom cost data were collected, average total cost over 12 weeks was $16,378 (95% CI, $14,620-$18,136) for the oral ciprofloxacin group and $20,569 (95% CI, $18,296-$22,842) for the IV ceftriaxone group, largely driven by lower average outpatient costs, as the average number of outpatient visits was halved for the oral ciprofloxacin group. There were no other statistically significant differences, either in inpatient costs or in other informal healthcare costs. Oral ciprofloxacin is less costly than IV ceftriaxone in the treatment of Klebsiella liver abscess, largely driven by reduced outpatient service costs.Trial registration: ClinicalTrials.gov Identifier NCT01723150 (7/11/2012).

Training infectious diseases senior residents during COVID-19: The impact and the lessons learnt.

BACKGROUND: The COVID-19 pandemic had major impact on the training of Infectious Diseases (ID) residents across the globe. They were part of the frontline staff, while at the same time training to be ID physicians. This study focused on identifying their capability, i.e. the ability to adapt existing competencies to new situations, which is now recognised as an essential element of professional practice. AIM: This study explored what ID residents learnt and how they learnt as they adapted to working in this unpredictable and challenging COVID-19 pandemic. METHODS: This qualitative explorative study was based in the Infectious Diseases Senior Residency Programme across three training institutions in Singapore. Individual semi-structured interviews were conducted. Data were analysed using a template analysis technique. RESULTS: Nine ID residents participated in this study. They learnt to engage with uncertainty in a meaningful way by relying on prior training and rapidly learning how to most effectively learn (metacognition). Learning was enhanced by collaboration between multidisciplinary health professionals, strong leadership and intrinsic motivation from personal interest in ID. They learnt through observing how senior faculty approached and managed the COVID-19 situation. CONCLUSION: When learning for future capability in a rapidly evolving situation, role-modelling and mentoring are essential as available information resources may still not provide the learning from skilled doctors with actual experiences managing complex, uncertain situations.

Review of the role of gastrointestinal multiplex polymerase chain reaction in the management of diarrheal illness.

Acute and chronic diarrheal illness secondary to gastrointestinal infection is a significant cause of morbidity and mortality around the world. A cornerstone of management includes prompt diagnosis and appropriate treatment of culprit pathogens. Timely diagnosis can improve patient care, assist in infection control, and prevent disease outbreaks. Historical methods of diagnosis include traditional culture methods and stool analysis. These are limited by long turnaround time and inability to simultaneously assess multiple pathogens. The advent of multiplexed nucleic acid amplification tests first began with the Food and Drug Administration-approved respiratory virus multiplex polymerase chain reaction (PCR) panel in 2009, followed by gastrointestinal infections in 2013, and neurological infections in 2014. We conducted a review of current literature pertaining to the clinical utility of a gastrointestinal multiplex PCR in management of acute and chronic diarrhea in patients. To date, seven platforms approved by the US Food and Drug Administration are used in detection of various bacterial, viral, and parasitic causative organisms for diagnosis of gastrointestinal infections. The sensitivity and specificity of each assay vary depending on the tested organism. Interpretation of a positive result has to be tailored to the clinical context. Further studies are required to establish the utility of gastrointestinal multiplex PCR from a cost-based perspective, whether specific enteropathogens such as Clostridioides difficile are better assessed with toxin gene detection and whether new parameters such as cycle threshold values can improve clinical application of test results.

Validation of Vancomycin Dosing Guidance During Transition of Care.

Vancomycin is an antibiotic commonly used to treat serious gram-positive infections. Patients requiring prolonged therapy in Singapore routinely receive intermittent vancomycin infusion in the hospital and are switched to continuous infusion for outpatient parenteral antibiotic therapy. During this transition of care, there may be a risk of not achieving therapeutic targets. We evaluated the performance of a model-based dosing algorithm in achieving a therapeutic target within 7 days of care transition. A published population pharmacokinetic model was used as the foundation to guide vancomycin dosing when discharging inpatients on intermittent infusion to outpatient care on continuous infusion. Selected demographic variables (age, weight, and creatinine clearance) were used to devise initial dosing. Patients with guided dosing were compared with historic controls (dosing by clinicians alone). The primary outcome of the study was to achieve vancomycin steady-state concentration of 20-25 mg/L. Compared with historic controls, the proportion of patients attaining a therapeutic target by day 7 was significantly improved (6 of 19 [31.6%] vs 12 of 17 [70.6%], P = .04). Our model-based approach could guide customized dosing to facilitate switching patients from intermittent to continuous infusion during transition of care. Further validation in a larger patient cohort is warranted.

The Pandemic Academy: Reflections of Infectious Diseases Fellows During COVID-19.

The COVID-19 pandemic has taken over the world at an unprecedented scale. As Infectious Diseases fellows, this has come straight into the heart of our specialty and created a unique impact on our training progress and perspective. Here, we reflect on our early experiences during the first three months of battling COVID-19 in Singapore and glean some lessons for this pandemic and beyond.

Coronavirus 2019 Silver Linings.

A heightened state of alert due to the Coronavirus Disease 2019 (COVID-19) outbreak was declared by the Singapore Ministry of Health on February 7, 2020. Within the hospital, team reorganizations, workflow revisions, and physical segregation caused anxiety among healthcare workers (HCWs). Fear of the unknown and emotional and physical fatigue started to take their toll on HCWs. We share our learning journey over the first 8 weeks of COVID-19: the importance of acknowledging fears and questions, and transforming them to collective knowledge; the role of empathic, hands-on leadership that brings camaraderie and calms scepticism; the importance of validating efforts and acknowledging hardship; and, most importantly, the security that comes from camaraderie, breaking down hierarchical barriers, and motivating each other to keep on going.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study.

BACKGROUND: Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. METHODS: This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. RESULTS: Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. CONCLUSIONS: Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. CLINICAL TRIALS REGISTRATION: NCT01723150.

An inactivated enterovirus 71 vaccine is safe and immunogenic in healthy adults: A phase I, double blind, randomized, placebo-controlled, study of two dosages.

BACKGROUND: Hand, foot and mouth disease (HFMD), especially that caused by enterovirus 71 (EV71) infection, is a public health concern in the Asia-Pacific region. We report a phase I clinical trial of an EV71 candidate vaccine (INV21) based on a binary ethylenimine inactivated B2 sub-genotype formulated with aluminum hydroxide. METHODS: In this double-blind, placebo-controlled, randomized, dose escalation study adult volunteers received two vaccinations 28 days apart of low or high dose formulations of the candidate vaccine and were then monitored for safety and reactogenicity for four weeks after each dose, and for their immune responses up to 28 weeks. RESULTS: Of 36 adults enrolled, 35 completed the study as planned. Either no or mild adverse events were observed, mainly injection site pain and tiredness. Seroconversion was 100% after two vaccinations. High geometric mean neutralizing antibody titers (GMT) were observed 14 days post first dose, peaking 14 days post second dose (at Day 42) in both high and low dose groups; GMTs on days 14, 28, 42, and 56 were 128, 81, 323, 203 and 144, 100, 451, 351 in low- and high-dose groups, respectively. Titers for both doses declined gradually to Day 196 but remained higher than baseline and the placebo groups, which had low GMTs throughout the duration of the study. Cross-neutralizing antibody activity against heterologous sub-genotypes was demonstrated. CONCLUSION: These data show that the EV71 candidate vaccine is safe and immunogenic in adults and supports further clinical development as a potential pediatric vaccine by initiating a dose-escalation study for determining the dose-dependent safety and immunogenicity of the vaccine in young naïve children.

Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study.

BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug-resistant organisms in healthcare settings worldwide, but little is known about MRSA transmission outside of acute healthcare settings especially in Asia. We describe the methods for a prospective longitudinal study of MRSA prevalence and transmission. METHODS: MRSA-colonized individuals were identified from MRSA admission screening at two tertiary hospitals and recruited together with their household contacts. Participants submitted self-collected nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and monthly thereafter for 6 months. A comparison group of households of MRSA-negative patients provided swab samples at one time point. In a validation sub-study, separate swabs from each site were collected from randomly selected individuals, to compare MRSA detection rates between swab sites, and between samples collected by participants versus those collected by trained research staff. Information on each participant's demographic information, medical status and medical history, past healthcare facilities usage and contacts, and personal interactions with others were collected using a self-administered questionnaire. DISCUSSION/CONCLUSION: Understanding the dynamics of MRSA persistence and transmission in the community is crucial to devising and evaluating successful MRSA control strategies. Close contact with MRSA colonized patients may to be important for MRSA persistence in the community; evidence from this study on the extent of community MRSA could inform the development of household- or community-based interventions to reduce MRSA colonization of close contacts and subsequent re-introduction of MRSA into healthcare settings. Analysis of longitudinal data using whole-genome sequencing will yield further information regarding MRSA transmission within households, with significant implications for MRSA infection control outside acute hospital settings.

Catheter-associated urinary tract infection.

PURPOSE OF REVIEW: Catheter-associated urinary tract infection (CAUTI) is the commonest nosocomial infection worldwide. Here we review the recent advances in the prevention of CAUTI. RECENT FINDINGS: After more than 30 years, new guidelines were issued in 2008-2011 by the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Healthcare Infection Control Practices Advisory Committee and European Association of Urology. These guidelines addressed novel technologies such as silver alloy or antimicrobial coatings on catheters, hydrophilic catheters, urethral stents, use of sealed catheter-tube junctions and antiinfective bladder irrigation. In addition, multiple trials have been published recently on the reduction of inappropriate urinary tract catheterization. SUMMARY: Numerous strategies have been developed to reduce the incidence of CAUTI but few have proven effective. Reducing the inappropriate use of catheters and development of novel technologies targeted against these increasingly multidrug-resistant pathogens may be useful in the prevention of CAUTI in our vulnerable patients.

Late relapse of non-typhoidal salmonella vascular graft infection after 5 years.

Salmonella bacteremia can be complicated by mycotic aneurysm with the potential for a catastrophic presentation. Treatment involves prompt surgery with debridement, extraanatomic bypass, and prolonged antibiotic therapy. Any relapse tends to occur within the 1(st) year after surgery. We describe a case of Salmonella enteritidis mycotic aneurysm in a 56-year-old man 5 years after the initial presentation, emphasizing the importance of aggressive initial therapy and long-term surveillance.